| http://purl.uniprot.org/citations/28974561 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28974561 | http://www.w3.org/2000/01/rdf-schema#comment | "The activity of Src family kinases (Src being the prototypical member) is tightly regulated by differential phosphorylation on Tyr416 (positive) and Tyr527 (negative), a duet that reciprocally regulates kinase activity. The latter negative regulation of Src on Tyr527 is mediated by C-terminal Src kinase (CSK) that phosphorylates Tyr527 and maintains Src in a clamped negative regulated state by promoting an intramolecular association. Here it is demonstrated that the SH2- and SH3-domain containing adaptor protein CrkII, by virtue of its phosphorylation on Tyr239, regulates the Csk/Src signaling axis to control Src activation. Once phosphorylated, the motif (PIpYARVIQ) forms a consensus sequence for the SH2 domain of CSK to form a pTyr239-CSK complex. Functionally, when expressed in Crk-/- MEFs or in Crk+/+ HS683 cells, Crk Y239F delayed PDGF-BB-inducible Src Tyr416 phosphorylation. Moreover, expression of Crk Y239F in HS683 cells delayed Src kinase activation and suppressed the cell-invasive and -transforming phenotypes. Finally, through loss-of-function and epistasis experiments using CRISPR-Cas9-engineered 4T1 murine breast cancer cells, Crk Tyr239 is implicated in breast cancer tumor growth and metastasis in orthotopic immunocompetent 4T1 mice model of breast adenocarcinoma. These findings delineate a novel role for Crk Tyr239 phosphorylation in the regulation of Src kinases, as well as a potential molecular explanation for a long-standing question as to how Crk regulates the activation of Src kinases.Implications: These findings provide new perspectives on the versatility of Crk in cancer by demonstrating how Crk mechanistically drives, through a tyrosine phosphorylation-dependent manner, tumor growth, and metastasis. Mol Cancer Res; 16(1); 173-83. ©2017 AACR."xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.org/dc/terms/identifier | "doi:10.1158/1541-7786.mcr-17-0242"xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/author | "Kumar S."xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/author | "Lu B."xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/author | "Machida K."xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/author | "Birge R.B."xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/author | "Hornbeck P."xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/author | "Davra V."xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/name | "Mol Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/pages | "173-183"xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/title | "Crk Tyrosine Phosphorylation Regulates PDGF-BB-inducible Src Activation and Breast Tumorigenicity and Metastasis."xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://purl.uniprot.org/core/volume | "16"xsd:string |
| http://purl.uniprot.org/citations/28974561 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28974561 |
| http://purl.uniprot.org/citations/28974561 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28974561 |
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| http://purl.uniprot.org/uniprot/#_Q8BPE7-mappedCitation-28974561 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28974561 |
| http://purl.uniprot.org/uniprot/#_Q5ND50-mappedCitation-28974561 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28974561 |
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| http://purl.uniprot.org/uniprot/#_P46108-mappedCitation-28974561 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28974561 |
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